Thanks - very interesting paper, Jeffrey.
I think your analysis is correct, but you forgot: (4) the skill of the
crystallographer...
Best wishes,
--Gerard
On Wed, 15 Jul 2020, Jeffrey B Bonanno wrote:
Hi Gerard and Bernhard,
As a postdoc in an unnamed small molecule lab, I was instructed by my lab head
to get better unit cell estimates prior to data collection owing to error
propagation from the uncertainty on cell dimensions through to the esd on
atomic bond lengths and angles when refining in shelxl. To verify this (what,
you believed everything your postdoc advisor told you?), I took a working
dataset and increased (only) the error on unit cell dimensions in the
instruction file for the final round of full matrix least squares refinement in
shelxl. Sure enough, the errors on the bonds and angles shot up. I was more
careful in determining the unit cell thereafter. That is, until, I became a
macromolecular crystallographer...
After an inciteful (sp? lol) discussion with Wladek about cell dimensions, I
was directed to read this paper:
Acta Crystallogr D Biol Crystallogr. 2015 Nov 1; 71(Pt 11): 2217–2226.
Have a look, it is interesting.
Having never followed up on these studies to see what happened to bonds and
angles in proteins and their ligands when varying cell dimensions, I can't
say with any confidence. However, I would guess that the quality of the
refined ligand coordinates could only be as good as some combination of
factors including but not limited to 1) the data (resolution, B factor,
etc), 2) the actual occupancy of the ligand, and 3) the restraints employed.
jbb
Jeffrey B. Bonanno, Ph.D.
Department of Biochemistry
Albert Einstein College of Medicine
1300 Morris Park Avenue
Bronx, NY 10461
off. 718-430-2452 fax. 718-430-8565
email jeffrey.bona...@einsteinmed.org
-----Original Message-----
From: CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> On Behalf Of Gerard DVD
Kleywegt
Sent: Wednesday, July 15, 2020 11:49 AM
To: CCP4BB@JISCMAIL.AC.UK
Subject: Re: [ccp4bb] Quote source inquiry
Well, I've had this in my CSHL X-ray Course talk for many years.
In the attached 2007 Acta D paper it says (p 95): "Macromolecular X-ray
crystallography is a notoriously poor method for determining the structure of small
molecules that are bound to macromolecules [...]" and then goes on to explain why
this is the case.
In the attached 2003 paper (pooling the wisdom of several of the usual
suspects, including Eleanor) it says something similar (p 1057):
"Coordinates of molecules that have been determined in complex with
macromolecules previously can of course also be retrieved from the PDB (Bernstein et
al., 1977; Berman et al., 2000), HIC-Up (Kleywegt and Jones, 1998), or CHEMPDB
(Boutselakis et al., 2003). However, one should keep in mind that these coordinates
are the result of refinement against comparatively
low-resolu- tion data where the small molecule constituted only a minute
fraction of the total scattering matter. This makes these coordinates
inherently much less accurate than those obtained from the CSD. In addition,
the coordi- nates may contain errors due to the use of incorrect restraints.
Hence, such coordinate sets should only be used as a last resort, and only
after verification that they are reliable. The latter can be facilitated by
inspection of the electron density for the compound in question, for instance
at the Uppsala Electron-Density Server (http:// fsrv1.bmc.uu.se/eds) (G.J.K.
et al., submitted)."
Happy to be confused with George though!
--Gerard (no, the other one)
On Tue, 14 Jul 2020, Bernhard Rupp wrote:
Hi Fellows,
afaicrimps (as far as I can recall in my progressing senility)
someone once wrote/stated/cursed somewhere that "Macromolecular
refinement is not a small molecule structure determination method".
Any citable source - George Sheldrick might be a suspect.
Thanks & best regards, BR
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